Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress

Vivek K. Gupta; Yuyi You; Alexander Klistorner; Stuart L. Graham

doi:10.1016/j.bbadis.2012.07.016

Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress

Vivek K. Gupta^*, Yuyi You, Alexander Klistorner, Stuart L. Graham

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

Tropomyosin-receptor-kinase B (TrkB receptor) activation plays an important role in the survival of retinal ganglion cells (RGCs). This study reports a novel finding that, SH2 domain. -containing phosphatase-2 (Shp-2) binds to the TrkB receptor in RGCs and negatively regulates its activity under glaucomatous stress. This enhanced binding of TrkB and Shp2 is mediated through caveolin. Caveolin 1 and 3 undergo hyper-phosphorylation in RGCs under stress and bind to the Shp2 phosphatase. Shp2 undergoes activation under glaucomatous stress conditions in RGCs in vivo with a concurrent loss of TrkB activity. Inhibiting the Shp2 phosphatase restored TrkB activity in cells exposed to excitotoxic and oxidative stress. Collectively, these findings implicate a molecular basis of Shp2 mediated TrkB deactivation leading to RGC degeneration observed in glaucoma.

Original language	English
Pages (from-to)	1643-1649
Number of pages	7
Journal	Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume	1822
Issue number	11
DOIs	https://doi.org/10.1016/j.bbadis.2012.07.016
Publication status	Published - Nov 2012

Access to Document

10.1016/j.bbadis.2012.07.016

Cite this

@article{855a42bd8f804d158390fe2c625da88b,

title = "Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress",

abstract = "Tropomyosin-receptor-kinase B (TrkB receptor) activation plays an important role in the survival of retinal ganglion cells (RGCs). This study reports a novel finding that, SH2 domain. -containing phosphatase-2 (Shp-2) binds to the TrkB receptor in RGCs and negatively regulates its activity under glaucomatous stress. This enhanced binding of TrkB and Shp2 is mediated through caveolin. Caveolin 1 and 3 undergo hyper-phosphorylation in RGCs under stress and bind to the Shp2 phosphatase. Shp2 undergoes activation under glaucomatous stress conditions in RGCs in vivo with a concurrent loss of TrkB activity. Inhibiting the Shp2 phosphatase restored TrkB activity in cells exposed to excitotoxic and oxidative stress. Collectively, these findings implicate a molecular basis of Shp2 mediated TrkB deactivation leading to RGC degeneration observed in glaucoma.",

author = "Gupta, {Vivek K.} and Yuyi You and Alexander Klistorner and Graham, {Stuart L.}",

year = "2012",

month = nov,

doi = "10.1016/j.bbadis.2012.07.016",

language = "English",

volume = "1822",

pages = "1643--1649",

journal = "Biochimica et Biophysica Acta - Molecular Basis of Disease",

issn = "0925-4439",

publisher = "Elsevier",

number = "11",

}

TY - JOUR

T1 - Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress

AU - Gupta, Vivek K.

AU - You, Yuyi

AU - Klistorner, Alexander

AU - Graham, Stuart L.

PY - 2012/11

Y1 - 2012/11

N2 - Tropomyosin-receptor-kinase B (TrkB receptor) activation plays an important role in the survival of retinal ganglion cells (RGCs). This study reports a novel finding that, SH2 domain. -containing phosphatase-2 (Shp-2) binds to the TrkB receptor in RGCs and negatively regulates its activity under glaucomatous stress. This enhanced binding of TrkB and Shp2 is mediated through caveolin. Caveolin 1 and 3 undergo hyper-phosphorylation in RGCs under stress and bind to the Shp2 phosphatase. Shp2 undergoes activation under glaucomatous stress conditions in RGCs in vivo with a concurrent loss of TrkB activity. Inhibiting the Shp2 phosphatase restored TrkB activity in cells exposed to excitotoxic and oxidative stress. Collectively, these findings implicate a molecular basis of Shp2 mediated TrkB deactivation leading to RGC degeneration observed in glaucoma.

AB - Tropomyosin-receptor-kinase B (TrkB receptor) activation plays an important role in the survival of retinal ganglion cells (RGCs). This study reports a novel finding that, SH2 domain. -containing phosphatase-2 (Shp-2) binds to the TrkB receptor in RGCs and negatively regulates its activity under glaucomatous stress. This enhanced binding of TrkB and Shp2 is mediated through caveolin. Caveolin 1 and 3 undergo hyper-phosphorylation in RGCs under stress and bind to the Shp2 phosphatase. Shp2 undergoes activation under glaucomatous stress conditions in RGCs in vivo with a concurrent loss of TrkB activity. Inhibiting the Shp2 phosphatase restored TrkB activity in cells exposed to excitotoxic and oxidative stress. Collectively, these findings implicate a molecular basis of Shp2 mediated TrkB deactivation leading to RGC degeneration observed in glaucoma.

UR - http://www.scopus.com/inward/record.url?scp=84865053645&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2012.07.016

DO - 10.1016/j.bbadis.2012.07.016

M3 - Article

C2 - 22878065

AN - SCOPUS:84865053645

VL - 1822

SP - 1643

EP - 1649

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

SN - 0925-4439

IS - 11

ER -

Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress

Abstract

Access to Document

Other files and links

Fingerprint

Cite this